Exploiting codon usage identifies intensity-specific modifiers of Ras/MAPK signaling in vivo |
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Authors: | Jessica K Sawyer Zahra Kabiri Ruth A Montague Scott R Allen Rebeccah Stewart Sarah V Paramore Erez Cohen Hamed Zaribafzadeh Christopher M Counter Donald T Fox |
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Institution: | 1. Department of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, United States of America;2. Department of Cell Biology, Duke University School of Medicine, Durham, North Carolina, United States of America;3. Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina, United States of America;The University of North Carolina at Chapel Hill, UNITED STATES |
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Abstract: | Signal transduction pathways are intricately fine-tuned to accomplish diverse biological processes. An example is the conserved Ras/mitogen-activated-protein-kinase (MAPK) pathway, which exhibits context-dependent signaling output dynamics and regulation. Here, by altering codon usage as a novel platform to control signaling output, we screened the Drosophila genome for modifiers specific to either weak or strong Ras-driven eye phenotypes. Our screen enriched for regions of the genome not previously connected with Ras phenotypic modification. We mapped the underlying gene from one modifier to the ribosomal gene RpS21. In multiple contexts, we show that RpS21 preferentially influences weak Ras/MAPK signaling outputs. These data show that codon usage manipulation can identify new, output-specific signaling regulators, and identify RpS21 as an in vivo Ras/MAPK phenotypic regulator. |
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